Overview of the Citric Acid Cycle / Kreb Cycle or TCA Cycle
The citric acid cycle occurs in the cristae or membrane folds of mitochondria.
The citric acid cycle is also known as the Krebs cycle or tricarboxylic acid (TCA) cycle. The various names given to the unique cyclic metabolic pathway is due to the following;
Tricarboxylic acid cycle: This pathway involves three carbon chains acids, from the start of the cycle where acetyl coA is diffused, to the end where oxaloacetate is regenerated. From the name itself, you will understand the reason. Hence, tri= 3, then the carboxylic acid involved.
Citric acid cycle: The reason behind this name is that, the first product or intermediate formed in this pathway is citrate or citric acid. This occurs when acetyl coA diffuse with oxaloacetate.
Kreb cycle: This is gotten from the name of the scientist that researched or found the pathway.
The pathway is a series of chemical reactions in the cell that breaks down food molecules into carbon dioxide, water, and energy. These reactions are piloted by several Biocatalysts; known as enzymes.
In plants and animals, these reactions take place in the matrix of the mitochondria of the cell as part of cellular respiration. Many bacteria perform the citric acid cycle too, though they do not have mitochondria so the reactions take place in the cytoplasm of bacterial cells.
In bacteria (prokaryotes), the plasma membrane of the cell is used to provide the proton gradient due to electromotive forces to produce ATP.
Sir Hans Adolf Krebs, a British biochemist, is credited with discovering the cycle. Sir Krebs outlined the steps of the cycle in 1937. For this reason, it is often called the Krebs cycle. It’s also known as the citric acid cycle, for the molecule that is consumed and then regenerated. Another name for citric acid is tricarboxylic acid, so the set of reactions is sometimes called the tricarboxylic acid cycle or TCA cycle.
Citric Acid Cycle Biochemical Reaction
The overall reaction for the citric acid cycle is represented below
Acetyl-CoA + 3 NAD+ + Q + GDP + Pi + 2 H2O → CoA-SH + 3 NADH + 3 H+ + QH2 + GTP + 2 CO2
where Q is ubiquinone and Pi is inorganic phosphate
The Citric Acid Cycle is also known as the Krebs Cycle or Tricarboxylic Acid (TCA) Cycle as stated previously. It is a series of biochemical reactions that takes place in the cell that breaks down food molecules into carbon dioxide, water, and energy.
In order for food to enter the citric acid cycle, it must be broken into acetyl groups, (CH3CO). The acetyl was produced after Glycolysis. In Glycolysis, glucose is converted to pyruvate. At the start of the citric acid cycle, an acetyl group combines with a four-carbon molecule called oxaloacetate to form a six-carbon compound, citric acid. During the cycle, the citric acid molecule is rearranged and stripped of two of its carbon atoms. Carbon dioxide and 4 electrons are released.
At the end of the cycle, a molecule of oxaloacetate is regenerated, which can combine with another acetyl group to begin the cycle again.
Substrate → Products (Enzyme)
Oxaloacetate + Acetyl CoA + H2O → Citrate + CoA-SH (citrate synthase)
In the above reaction, a molecule of acetyl CoA condenses with oxaloacetate. The product intermediate in this step is citrate. The coA is stripped off from acetyl to yield a coA-SH. The enzyme in this step of tricarboxylic acid cycle (TCA cycle) is citrate synthase.
Citrate → cis-Aconitate + H2O (aconitase)
In the step above, aconitase will strip water molecule off from citrate to yield cis-aconitate. The enzyme perform a two step reaction in this step of citric acid cycle. The first half reaction will yield cis-aconitate. Then, aconitate is isomerized to yield isocitrate which is the next reaction.
cis-Aconitate + H2O → Isocitrate (aconitase)
Isocitrate + NAD+ Oxalosuccinate + NADH + H + (isocitrate dehydrogenase)
In the reaction above, the enzyme; isocitrate dehydrogenase removes two Hydrogen atoms from isocitrate. Oxidized NAD+ is reduced by accepting the Hydrogen atoms from isocitrate. The intermediate formed in this step is oxalosuccinate.
Oxalosuccinate -> α-Ketoglutarate + CO2 (isocitrate dehydrogenase)
In this step of TCA cycle, the former intermediate; oxalosuccinate is decarboxylated to yield alpha- ketoglutarate. The enzyme that pilots this step is isocitrate dehydrogenase.
α-Ketoglutarate + NAD+ + CoA-SH → Succinyl-CoA + NADH + H+ + CO2 (α-ketoglutarate dehydrogenase)
In the above step of kreb cycle, the former intermediate is dehydrogenated and decarboxylated, with the addition of an coA-SH radical. The product intermediate is succinyl-CoA a-ketoglutarate dehydrogenase as the enzyme.
Succinyl-CoA + GDP + Pi → Succinate + CoA-SH + GTP (succinyl-CoA synthetase)
In the above step of citric acid cycle, the first energy molecule is formed. The inorganic phosphate (Pi) is gotten from the environment. The coA-SH is also liberated in this process or step. The enzyme responsible for the process is succinyl-CoA synthetase.
Note: there is a difference between a synthase and synthetase enzyme.
Succinate + ubiquinone (Q) → Fumarate + ubiquinol (QH2) (succinate dehydrogenase)
In the above step of TCA cycle, succinate is dehydrogenated to form fumerate. The molecule accepting the liberated hydrogen molecule in this step is ubiquinone, denoted by Q. The ubiquinone on accepting the the hydrogen molecule will become ubiquinol. The enzyme for this step is succinate dehydrogenase.
Fumarate + H2O → L-Malate (fumarase)
In the above step of kreb cycle, fumarate is hydrated to form L-Malate. The enzyme responsible is fumarase.
L-Malate + NAD+ → Oxaloacetate + NADH + H+ (malate dehydrogenase)
In this last step of TCA cycle, oxaloacetate is regenerated. The enzyme responsible is malate dehydrogenase.
Functions of the Krebs Cycle
Citric acid is also known as 2-hydroxypropane-1,2,3-
The Krebs cycle is the key set of reactions for aerobic cellular respiration. Some of the important functions of the cycle include:
- It is used to obtain chemical energy from proteins, fats, and carbohydrates. ATP is the energy molecule that is produced. The net ATP gain is 28 ATP per cycle (compared with 2 ATP for glycolysis, 28 ATP for oxidative phosphorylation, and 2 ATP for fermentation). In other words, the Krebs cycle connects fat, protein, and carbohydrate metabolism.
- The cycle can be used to synthesize precursors for amino acids. The precursors are aminated to yield amino acids.
- The reactions produce the molecule NADH, which is a reducing agent used in a variety of biochemical reactions.
- The citric acid cycle reduces flavin adenine dinucleotide (FADH), another source of energy.
Origin of the Krebs Cycle
The citric acid cycle or Krebs cycle isn’t the only set of chemical reactions cells could use to release chemical energy, however, it is the most efficient. It’s possible the cycle has abiogenic origins, predating life. It’s possible the cycle evolved more than one time. Part of the cycle comes from reactions that occur in anaerobic bacteria.
For a better understanding of this topic, read up photosynthesis.
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